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	Kinase Fusion Gene Summary
	Kinase Fusion Gene Sample Information
	Kinase Fusion ORF Analysis
	Kinase Fusion Amino Acid Sequences
	Multiple Sequence Alignment of All Fusion Protein Isoforms
	Kinase Fusion Protein Functional Features
	Kinase Fusion Protein Structures
	Comparison of Fusion Protein Isoforms
	Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB
	pLDDT Scores and Difference Analysis of pLDDT Scores Between the Active Sites (Best) and Non-Active Sites.
	Ramachandran Plot of Kinase Fusion Protein Structure
	Potential Active Site Information
	Virtual Screening Results
	Kinase-Substrate Information
	Related Drugs with This Kinase Fusion Protein
	Related Disease with This Kinase Fusion Protein
	Clinical Trials of the Found Drugs/Small Molecules

Kinase Fusion Gene:TMEM165_PDGFRA

Kinase Fusion Protein Summary

Kinase Fusion gene summary

Kinase Fusion partner gene information	Kinase Fusion gene name: TMEM165_PDGFRA
	KinaseFusionDB ID: KFG6616
	FusionGDB2.0 ID: KFG6616
		Hgene	Tgene
	Gene symbol	TMEM165	PDGFRA
	Gene ID	55858	5156
	Gene name	transmembrane protein 165	platelet derived growth factor receptor alpha
	Synonyms	CDG2K\|FT27\|GDT1\|SLC64A1\|TMPT27\|TPARL	CD140A\|PDGFR-2\|PDGFR2
	Cytomap	4q12	4q12
	Type of gene	protein-coding	protein-coding
	Description	putative divalent cation/proton antiporter TMEM165transmembrane protein 165TPA regulated locustransmembrane protein PT27transmembrane protein TPARL	platelet-derived growth factor receptor alphaCD140 antigen-like family member ACD140a antigenPDGF-R-alphaalpha-type platelet-derived growth factor receptorplatelet-derived growth factor receptor 2platelet-derived growth factor receptor, alpha polype
	Modification date	20240407	20240416
	UniProtAcc	Q9HC07	P16234
Ensembl transtripts involved in fusion gene	ENST ids	ENST00000381334, ENST00000506198, ENST00000542052, ENST00000514904,	ENST00000508170, ENST00000257290,
Context (manual curation of fusion genes in KinaseFusionDB)	PubMed: TMEM165 [Title/Abstract] AND PDGFRA [Title/Abstract] AND fusion [Title/Abstract]
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)	TMEM165(56262563)-PDGFRA(55133456), # samples:4

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	TMEM165	GO:0006816	calcium ion transport	32047108
Hgene	TMEM165	GO:0006828	manganese ion transport	32047108
Hgene	TMEM165	GO:0032472	Golgi calcium ion transport	23569283
Tgene	PDGFRA	GO:0008284	positive regulation of cell population proliferation	10806482
Tgene	PDGFRA	GO:0010544	negative regulation of platelet activation	8188664
Tgene	PDGFRA	GO:0018108	peptidyl-tyrosine phosphorylation	2536956\|8188664
Tgene	PDGFRA	GO:0030335	positive regulation of cell migration	17470632
Tgene	PDGFRA	GO:0034614	cellular response to reactive oxygen species	24190966
Tgene	PDGFRA	GO:0038091	positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	17470632
Tgene	PDGFRA	GO:0046777	protein autophosphorylation	2536956\|8188664
Tgene	PDGFRA	GO:0048008	platelet-derived growth factor receptor signaling pathway	2536956\|10806482
Tgene	PDGFRA	GO:0048146	positive regulation of fibroblast proliferation	10806482

Kinase Fusion gene breakpoints across TMEM165 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Kinase Fusion gene breakpoints across PDGFRA (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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Kinase Fusion Gene Sample Information

Kinase Fusion gene information.

Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE)
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.

Source	Sample	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp
ChimerDB4	TCGA-06-2559-01A	TMEM165	chr4	56262563	PDGFRA	chr4	55133456
ChimerDB4	TCGA-06-2559	TMEM165	chr4	56262563	PDGFRA	chr4	55133455

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Kinase Fusion ORF Analysis

Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB.

Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	Seq length (transcript)	Seq length (amino acids)
ENST00000506198	ENST00000257290	TMEM165	chr4	56262563	PDGFRA	chr4	55133456	5926	930
ENST00000506198	ENST00000257290	TMEM165	chr4	56262563	PDGFRA	chr4	55133455	5926	930

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Kinase Fusion Amino Acid Sequences

For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones.

>Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq

>ENST00000506198_ENST00000257290_TMEM165_chr4_56262563_PDGFRA_chr4_55133456_length(amino acids)=930
MFGVEASRRRHFLLRRPCAAGPAGGMAAAAPGNGRASAPRLLLLFLVPLLWAPAAVRAGPDEDLSHRNKEPPAPAQQLQPQPVAVQGPEP
ARVEKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVKEMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEV
RAYPPPRISWLKNNLTLIENLTEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDLVDDHHGSTG
GQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRDRSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAP
TLRSELTVAAAVLVLLVIVIISLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLGSGAFGKVVE
GTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNLLGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPE
KPKKELDIFGLNPADESTRSYVILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKNLLSDDNSEG
LTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVW
SYGILLWEIFSLGGTPYPGMMVDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKKSYEKIHLDF
LKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYIIPLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTF

--------------------------------------------------------------

>ENST00000506198_ENST00000257290_TMEM165_chr4_56262563_PDGFRA_chr4_55133455_length(amino acids)=930
MFGVEASRRRHFLLRRPCAAGPAGGMAAAAPGNGRASAPRLLLLFLVPLLWAPAAVRAGPDEDLSHRNKEPPAPAQQLQPQPVAVQGPEP
ARVEKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVKEMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEV
RAYPPPRISWLKNNLTLIENLTEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDLVDDHHGSTG
GQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRDRSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAP
TLRSELTVAAAVLVLLVIVIISLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLGSGAFGKVVE
GTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNLLGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPE
KPKKELDIFGLNPADESTRSYVILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKNLLSDDNSEG
LTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVW
SYGILLWEIFSLGGTPYPGMMVDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKKSYEKIHLDF
LKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYIIPLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTF

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Multiple Sequence Alignment of All Fusion Protein Isoforms

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Kinase Fusion Protein Functional Features

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr4:56262563/chr4:55133456)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
TMEM165 Q9HC07	PDGFRA P16234
FUNCTION: Putative divalent cation:proton antiporter that exchanges calcium or manganese ions for protons across the Golgi membrane. Mediates the reversible transport of calcium or manganese to the Golgi lumen driven by the proton gradient and possibly the membrane potential generated by V-ATPase. Provides calcium or manganese cofactors to resident Golgi enzymes and contributes to the maintenance of an acidic luminal Golgi pH required for proper functioning of the secretory pathway (PubMed:32047108, PubMed:23569283, PubMed:22683087, PubMed:27008884) (By similarity). Promotes Ca(2+) storage within the Golgi lumen of the mammary epithelial cells to be then secreted into milk (By similarity). The transport mechanism and stoichiometry remains to be elucidated. {ECO:0000250\|UniProtKB:P38301, ECO:0000250\|UniProtKB:P52875, ECO:0000269\|PubMed:22683087, ECO:0000269\|PubMed:23569283, ECO:0000269\|PubMed:27008884, ECO:0000269\|PubMed:32047108}.	FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269\|PubMed:10734113, ECO:0000269\|PubMed:10947961, ECO:0000269\|PubMed:11297552, ECO:0000269\|PubMed:12522257, ECO:0000269\|PubMed:1646396, ECO:0000269\|PubMed:17087943, ECO:0000269\|PubMed:1709159, ECO:0000269\|PubMed:17141222, ECO:0000269\|PubMed:20972453, ECO:0000269\|PubMed:21224473, ECO:0000269\|PubMed:21596750, ECO:0000269\|PubMed:2554309, ECO:0000269\|PubMed:8188664, ECO:0000269\|PubMed:8760137, ECO:0000269\|PubMed:8943348}.

Retention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at
download page
* Minus value of BPloci means that the break pointn is located before the CDS.

- Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt).

Partner

Hgeneene

Hbp

Tgeneene

Tbp

ENST

BPexon

TotalExon

Protein feature loci

BPloci

TotalLen

Feature

Note

- Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt).

Partner	Hgeneene	Hbp	Tgeneene	Tbp	ENST	BPexon	TotalExon	Protein feature loci	BPloci	TotalLen	Feature	Note
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	0	4	24_113	0	219	Domain	Note=Ig-like C2-type 1
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	0	4	24_113	0	219	Domain	Note=Ig-like C2-type 1
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	0	4	117_201	0	219	Domain	Note=Ig-like C2-type 2
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	0	4	117_201	0	219	Domain	Note=Ig-like C2-type 2
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	0	4	202_306	0	219	Domain	Note=Ig-like C2-type 3
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	0	4	202_306	0	219	Domain	Note=Ig-like C2-type 3
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	0	4	319_410	0	219	Domain	Note=Ig-like C2-type 4
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	4	23	319_410	253	1090	Domain	Note=Ig-like C2-type 4
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	0	4	319_410	0	219	Domain	Note=Ig-like C2-type 4
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	4	23	319_410	253	1090	Domain	Note=Ig-like C2-type 4
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	0	4	414_517	0	219	Domain	Note=Ig-like C2-type 5
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	4	23	414_517	253	1090	Domain	Note=Ig-like C2-type 5
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	0	4	414_517	0	219	Domain	Note=Ig-like C2-type 5
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	4	23	414_517	253	1090	Domain	Note=Ig-like C2-type 5
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	0	4	593_954	0	219	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	TMEM165	56262563	PDGFRA	55133455	ENST00000506198	4	23	593_954	253	1090	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	0	4	593_954	0	219	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159
Tgene	TMEM165	56262563	PDGFRA	55133456	ENST00000506198	4	23	593_954	253	1090	Domain	Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255\|PROSITE-ProRule:PRU00159

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Kinase Fusion Protein Structures

CIF files of the predicted kinase fusion proteins
* Here we show the 3D structure of the fusion proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.

Kinase Fusion protein CIF link (fusion AA seq ID in KinaseFusionDB)	Henst	Tenst	Hgene	Hchr	Hbp	Tgene	Tchr	Tbp	AA seq	Len(AA seq)
PDB file >>>511_TMEM165_PDGFRA	ENST00000506198	ENST00000257290	TMEM165	chr4	56262563	PDGFRA	chr4	55133455	MFGVEASRRRHFLLRRPCAAGPAGGMAAAAPGNGRASAPRLLLLFLVPLLWAPAAVRAGPDEDLSHRNKEPPAPAQQLQPQPVAVQGPEP ARVEKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVKEMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEV RAYPPPRISWLKNNLTLIENLTEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDLVDDHHGSTG GQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRDRSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAP TLRSELTVAAAVLVLLVIVIISLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLGSGAFGKVVE GTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNLLGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPE KPKKELDIFGLNPADESTRSYVILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKNLLSDDNSEG LTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVW SYGILLWEIFSLGGTPYPGMMVDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKKSYEKIHLDF LKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYIIPLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTF	930
3D view using mol* of 511_TMEM165_PDGFRA

PDB file >>>TKFP_865_TMEM165_PDGFRA	ENST00000506198	ENST00000257290	TMEM165	chr4	56262563	PDGFRA	chr4	55133456	MFGVEASRRRHFLLRRPCAAGPAGGMAAAAPGNGRASAPRLLLLFLVPLLWAPAAVRAGPDEDLSHRNKEPPAPAQQLQPQPVAVQGPEP ARVEKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVKEMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEV RAYPPPRISWLKNNLTLIENLTEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDLVDDHHGSTG GQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRDRSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAP TLRSELTVAAAVLVLLVIVIISLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLGSGAFGKVVE GTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNLLGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPE KPKKELDIFGLNPADESTRSYVILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKNLLSDDNSEG LTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVW SYGILLWEIFSLGGTPYPGMMVDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKKSYEKIHLDF LKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYIIPLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTF	930_TMEM165_PDGFRA
PDB file >>>TKFP_866_TMEM165_PDGFRA	ENST00000506198	ENST00000257290	TMEM165	chr4	56262563	PDGFRA	chr4	55133455	MFGVEASRRRHFLLRRPCAAGPAGGMAAAAPGNGRASAPRLLLLFLVPLLWAPAAVRAGPDEDLSHRNKEPPAPAQQLQPQPVAVQGPEP ARVEKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVKEMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEV RAYPPPRISWLKNNLTLIENLTEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDLVDDHHGSTG GQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRDRSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAP TLRSELTVAAAVLVLLVIVIISLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLGSGAFGKVVE GTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNLLGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPE KPKKELDIFGLNPADESTRSYVILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKNLLSDDNSEG LTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLARDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVW SYGILLWEIFSLGGTPYPGMMVDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKKSYEKIHLDF LKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYIIPLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTF	930_TMEM165_PDGFRA

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Comparison of Fusion Protein Isoforms

Superimpose the 3D Structures Among All Fusion Protein Isoforms
* Download the pdb file and open it from the molstar online viewer.

Comparison of the Secondary Structures of Fusion Protein Isoforms

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Comparison of Fusion Protein Sequences/Structures with Known Sequences/Structures from PDB

TMEM165_PDGFRA does not have any known PDB structures.

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pLDDT score distribution

all_data/KinaseFusionDB_T_Results/KinaseFusionDB_T_ViolinPlots/511_TMEM165_PDGFRA.png

pLDDT score distribution of the predicted fusion protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
* The blue color at the bottom marks the best active site residues.

511_TMEM165_PDGFRA.png

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Potential Active Site Information

The potential binding sites of these fusion proteins were identified using SiteMap, a module of the Schrodinger suite.

Kinase Fusion AA seq ID in KinaseFusionDB

Site score

Size

Dscore

Volume

Exposure

Enclosure

Contact

Phobic

Philic

Balance

Don/Acc

Residues

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Ramachandran Plot of Kinase Fusion Protein Structure

Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this fusion protein peptide.

511_TMEM165_PDGFRA_ramachandran.png

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Virtual Screening Results

Distribution of the average docking score across all approved kinase inhibitors.
Distribution of the number of occurrence across all approved kinase inhibitors.

5'-kinase fusion protein case

3'-kinase fusion protein case

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Drug information from DrugBank of the top 20 interacting small molecules.
* The detailed information of individual kinase inhibitors are available in the download page.

Fusion gene name info	Drug	Docking score	Glide g score	Glide energy
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Tofacitinib	-7.135330000000001	-7.1468300000000005	-34.2714
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Tofacitinib	-7.135330000000001	-7.1468300000000005	-34.2714
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Asciminib	-6.60158	-6.96468	-28.3442
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Asciminib	-6.54955	-6.91265	-28.6929
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Tofacitinib	-6.5323400000000005	-6.54384	-34.6921
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Tofacitinib	-6.5323400000000005	-6.54384	-34.6921
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Sorafenib	-6.5207	-6.5328	-46.4335
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Sorafenib	-6.5207	-6.5328	-46.4335
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Larotrectinib	-6.5001	-6.5001	-42.3975
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Neratinib	-6.37737	-6.563269999999999	-31.9611
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Ripretinib	-6.363230000000001	-6.37023	-13.85
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Ripretinib	-6.363230000000001	-6.37023	-13.85
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Asciminib	-6.30322	-6.66632	-27.7804
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Neratinib	-6.296119999999999	-6.47842	-30.3453
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Neratinib	-6.296119999999999	-6.47842	-30.3453
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Ruxolitinib	-6.2884	-6.2884	-13.8646
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Lapatinib	-6.1378699999999995	-6.2266699999999995	-45.568999999999996
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Pralsetinib	-6.10838	-6.19988	-37.3118
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Regorafenib	-6.06462	-6.06462	-50.985
511_TMEM165_PDGFRA-DOCK_HTVS_1-001	Neratinib	-5.96528	-6.86758	-29.5012

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Kinase-Substrate Information of TMEM165_PDGFRA

Phosphorylation target of the kinase
(phosphosite, 03-17-2024)

Kinase	Kinase UniProt Acc	Kinase species	Substrate	Substrate UniProt Acc	Substrate phosphorylated residues	Substrate phosphorylated sites (+/-7AA)	Domain
PDGFRA	P16234	human	PDGFRA	P16234	Y1018	RLSADsGyIIPLPDI
PDGFRA	P16234	human	PDGFRA	P16234	Y572	IsPDGHEyIyVDPMQ
PDGFRA	P16234	human	PDGFRA	P16234	Y988	RVDSDNAyIGVtyKN
PDGFRA	P16234	human	CCDC88C	Q9P219	Y2025	PQTVWyEyGCV____
PDGFRA	P16234	human	SRC	P12931	Y419	RLIEDNEytARQGAk	PK_Tyr_Ser-Thr
PDGFRA	P16234	human	PDGFRA	P16234	Y574	PDGHEyIyVDPMQLP

Biological Network Integration of This Kinase and Substrates
(GeneMANIA website)

Enriched GO biological processes of the phosphorylation target genes of the kinase

Kinase	GOID	GO term	P.adjust
PDGFRA	ID	Description	0.00e+00
PDGFRA	GO:0031648	protein destabilization	4.83e-03
PDGFRA	GO:0022602	ovulation cycle process	4.83e-03
PDGFRA	GO:0048008	platelet-derived growth factor receptor signaling pathway	4.83e-03
PDGFRA	GO:0042698	ovulation cycle	5.44e-03
PDGFRA	GO:0008585	female gonad development	7.79e-03
PDGFRA	GO:0046545	development of primary female sexual characteristics	7.79e-03
PDGFRA	GO:0046660	female sex differentiation	7.79e-03
PDGFRA	GO:0042476	odontogenesis	7.79e-03
PDGFRA	GO:0030168	platelet activation	7.79e-03
PDGFRA	GO:0048565	digestive tract development	7.79e-03
PDGFRA	GO:0055123	digestive system development	8.41e-03
PDGFRA	GO:0034614	cellular response to reactive oxygen species	8.57e-03
PDGFRA	GO:0051897	positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	9.76e-03
PDGFRA	GO:0046777	protein autophosphorylation	1.07e-02
PDGFRA	GO:0000302	response to reactive oxygen species	1.07e-02
PDGFRA	GO:0031032	actomyosin structure organization	1.07e-02
PDGFRA	GO:0002064	epithelial cell development	1.07e-02
PDGFRA	GO:0070374	positive regulation of ERK1 and ERK2 cascade	1.07e-02
PDGFRA	GO:0007596	blood coagulation	1.07e-02
PDGFRA	GO:0050817	coagulation	1.07e-02
PDGFRA	GO:0007599	hemostasis	1.07e-02
PDGFRA	GO:0008406	gonad development	1.07e-02
PDGFRA	GO:0045137	development of primary sexual characteristics	1.07e-02
PDGFRA	GO:0051896	regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1.11e-02
PDGFRA	GO:0034599	cellular response to oxidative stress	1.13e-02
PDGFRA	GO:0060828	regulation of canonical Wnt signaling pathway	1.14e-02
PDGFRA	GO:0018108	peptidyl-tyrosine phosphorylation	1.20e-02
PDGFRA	GO:0018212	peptidyl-tyrosine modification	1.20e-02
PDGFRA	GO:0007548	sex differentiation	1.21e-02
PDGFRA	GO:0043491	phosphatidylinositol 3-kinase/protein kinase B signal transduction	1.21e-02
PDGFRA	GO:0048511	rhythmic process	1.21e-02
PDGFRA	GO:0048608	reproductive structure development	1.21e-02
PDGFRA	GO:0061458	reproductive system development	1.21e-02
PDGFRA	GO:0070372	regulation of ERK1 and ERK2 cascade	1.21e-02
PDGFRA	GO:0060070	canonical Wnt signaling pathway	1.21e-02
PDGFRA	GO:0062197	cellular response to chemical stress	1.21e-02
PDGFRA	GO:0031647	regulation of protein stability	1.24e-02
PDGFRA	GO:0070371	ERK1 and ERK2 cascade	1.24e-02
PDGFRA	GO:0033674	positive regulation of kinase activity	1.24e-02
PDGFRA	GO:0030111	regulation of Wnt signaling pathway	1.24e-02
PDGFRA	GO:0050878	regulation of body fluid levels	1.40e-02
PDGFRA	GO:0006979	response to oxidative stress	1.61e-02
PDGFRA	GO:0140694	non-membrane-bounded organelle assembly	1.61e-02
PDGFRA	GO:0051347	positive regulation of transferase activity	1.61e-02
PDGFRA	GO:0042060	wound healing	1.61e-02
PDGFRA	GO:0035332	positive regulation of hippo signaling	1.61e-02
PDGFRA	GO:0036093	germ cell proliferation	1.61e-02
PDGFRA	GO:0071803	positive regulation of podosome assembly	1.61e-02
PDGFRA	GO:0048732	gland development	1.61e-02

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Related Drugs to TMEM165_PDGFRA

Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Drug

Source

PMID

Distribution of the number of studies mentioning TMEM165-PDGFRA and kinase inhibitors the PubMed Abstract (04-01-2024)

Fusion gene - drug pair 1

Fusion gene - drug pair 2

PMID

Publication date

DOI

Study title

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Related Diseases to TMEM165_PDGFRA

Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)

Hgene

Tgene

Disease

Source

PMID

Related diseases from the literature mentioned this fusion gene and drug.
(PubMed, 04-01-2024)

MeSH ID

MeSH term

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner	Gene	Disease ID	Disease name	# pubmeds	Source
Tgene	PDGFRA	C0238198	Gastrointestinal Stromal Tumors	10	CGI;CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT
Tgene	PDGFRA	C3179349	Gastrointestinal Stromal Sarcoma	9	CLINGEN;CTD_human;ORPHANET
Tgene	PDGFRA	C0346421	Chronic eosinophilic leukemia	4	ORPHANET
Tgene	PDGFRA	C0206141	Idiopathic Hypereosinophilic Syndrome	3	CTD_human;GENOMICS_ENGLAND
Tgene	PDGFRA	C0006413	Burkitt Lymphoma	2	ORPHANET
Tgene	PDGFRA	C0206142	Eosinophilic leukemia	2	CTD_human
Tgene	PDGFRA	C0206143	Loeffler's Endocarditis	2	CTD_human
Tgene	PDGFRA	C1292769	Precursor B-cell lymphoblastic leukemia	2	ORPHANET
Tgene	PDGFRA	C1540912	Hypereosinophilic syndrome	2	CGI;CTD_human

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Clinical Trials of the Found Drugs/Small Molecules

Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024)

Clinical Trials from clinicaltrials.gov (06-17-2024)

Fusion Gene

Kinase Inhibitor

NCT ID

Study Status

Phases

Disease

# Enrolment

Date